Glioma cell activation by Alzheimer's peptide Aβ _1–42, α ₁-antichymotrypsin, and their mixture

Abstract.

We compared the effects of Alzheimer's peptide (Aβ _1–42), α ₁-antichymotrypsin (ACT) and an ACT/Aβ _1–42 mixture on human glioma DK-MG cells. The solution of Aβ (5 μM) formed by 2-h incubation at room temperature induced tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 levels by 55 and 45%, respectively, and increased gelatinase B activity by 67%, while exposure of cells to the ACT/Aβ _1–42 mixture (1:10 molar ratio ACT: Aβ _1–42) under the same experimental conditions showed no effect on IL-6 levels or gelatinase B activity, but strongly induced TNF-α (by 190%), compared to the controls. Stimulation of the cells with Aβ _1–42 alone, but not with ACT, increased by about 20% low-density lipoprotein (LDL) uptake and mRNA levels for LDL receptor and HMG-CoA reductase, while the ACT/Aβ _1–42 mixture significantly increased LDL uptake (by 50%), up-regulated mRNA levels for LDL receptor and HMG-CoA reductase by 48 and 63%, respectively, and increased lipid accumulation by about 20-fold. These data suggest a possible new role for Aβ in Alzheimer's disease through its interaction with the inflammatory reactant, ACT.